Revealing how transcriptional bursting kinetics are genomically encoded is challenging because genome structures are stochastic at the organization level and are suggestively linked to gene transcription. To address this challenge, we develop a generic theoretical framework that integrates chromatin dynamics, enhancer–promoter (E-P) communication, and gene-state switching to study transcriptional bursting. The theory predicts that power law can be a general rule to quantitatively describe bursting modulations by E-P spatial communication. Specifically, burst frequency and burst size are up-regulated by E-P communication strength, following power laws with positive exponents. Analysis of the scaling exponents further reveals that burst frequency is preferentially regulated. Bursting kinetics are down-regulated by E-P genomic distance with negative power-law exponents, and this negative modulation desensitizes at large distances. The mutual information between burst frequency (or burst size) and E-P spatial distance further reveals essential characteristics of the information transfer from E-P communication to transcriptional bursting kinetics. These findings, which are in agreement with experimental observations, not only reveal fundamental principles of E-P communication in transcriptional bursting but also are essential for understanding cellular decision-making.

中文翻译：

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增强子-启动子通讯调控转录爆发的幂律行为

揭示转录爆发动力学如何在基因组上编码具有挑战性，因为基因组结构在组织水平上是随机的，并且与基因转录有暗示性的联系。为了应对这一挑战，我们开发了一个通用的理论框架，整合了染色质动力学、增强子-启动子（EP）通讯和基因状态转换来研究转录爆发。该理论预测幂律可以成为定量描述EP空间通信突发调制的通用规则。具体来说，突发频率和突发大小由 EP 通信强度上调，遵循正指数幂律。对缩放指数的分析进一步表明突发频率受到优先调节。爆发动力学受到具有负幂律指数的 EP 基因组距离的下调，并且这种负调节在大距离下不敏感。突发频率（或突发大小）和 EP 空间距离之间的互信息进一步揭示了从 EP 通信到转录突发动力学的信息传递的基本特征。这些发现与实验观察结果一致，不仅揭示了转录爆发中 EP 通讯的基本原理，而且对于理解细胞决策至关重要。